Affiliation: Department of Psychology, University at Albany-SUNY Albany, NY, USA.

ABSTRACTSome hippocampally-influenced affective and/or cognitive processes decline with aging. The role of androgens in this process is of interest. Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol). To determine the extent to which some age-related decline in hippocampally-influenced behaviors may be due to androgens, we examined the effects of variation in androgen levels due to age, gonadectomy, and androgen replacement on cognitive (inhibitory avoidance, Morris water maze) and affective (defensive freezing, forced swim) behavior among young (4 months), middle-aged (13 months), and aged (24 months) male rats. Plasma and hippocampal levels of androgens were determined. In experiment 1, comparisons were made between 4-, 13-, and 24-month-old rats that were intact or gonadectomized (GDX) and administered a T-filled or empty silastic capsule. There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels. Chronic, long-term (1-4 weeks) T-replacement reversed the effects of GDX in 4- and 13-month-old, but not 24-month-old, rats in the inhibitory avoidance task. Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age. Thus, age is associated with a decrease in 3alpha-diol production and 3alpha-diol administration reinstates cognitive and affective performance of aged male rats.

Mentions:
The Morris Water Maze was used to assess hippocampally-influenced cognitive performance (Bennett et al., 2006). Day One (Habituation): A large circular water tank (175 cm diameter, 71 cm deep) was filled with water (20–25°C), and visually divided into four quadrants. White toxic-free tempera paint was added to the water to make it appear opaque. Rats were placed one at a time into the pool, without the platform in it, to become habituated to swimming for 1 min each. Day Two (Training): A clear Plexiglas platform (5.3 cm × 5.3 cm) was placed in one of the quadrants, 30 cm from the side of the pool and 2.5 cm below the surface of the water. White toxic-free tempera paint was added to the water to make it appear opaque and obscure the platform. The rat was placed in one of the four quadrants of the pool and given 2 min to find the hidden platform on two training trials. If the rat did not find the platform, it was placed on the platform by the experimenter. The rat remained on the platform for 45 s after reaching it. Day Three (Testing): The pool was filled to the same height, with the platform placed in the original location in the pool. Tempera paint was added and the rat was placed into one of the quadrants. Quadrant placement was counterbalanced across four trials. The amount of time it took the animal to find the hidden platform, and the distances traveled in the maze before finding it, were considered indices of performance on Day Three. On each trial, if the rat did not find the platform, it was placed on the platform by the experimenter. The rat remained on the platform for 45 s after reaching it. The mean latencies for rats to reach the platform across trials is indicated in insets in Figures 1, 3, and 5 to demonstrate learning curves for rats using this measure. During both training and testing, the distances swam in the pool and the latencies were used to calculate the average swim speed in each trial.

Mentions:
The Morris Water Maze was used to assess hippocampally-influenced cognitive performance (Bennett et al., 2006). Day One (Habituation): A large circular water tank (175 cm diameter, 71 cm deep) was filled with water (20–25°C), and visually divided into four quadrants. White toxic-free tempera paint was added to the water to make it appear opaque. Rats were placed one at a time into the pool, without the platform in it, to become habituated to swimming for 1 min each. Day Two (Training): A clear Plexiglas platform (5.3 cm × 5.3 cm) was placed in one of the quadrants, 30 cm from the side of the pool and 2.5 cm below the surface of the water. White toxic-free tempera paint was added to the water to make it appear opaque and obscure the platform. The rat was placed in one of the four quadrants of the pool and given 2 min to find the hidden platform on two training trials. If the rat did not find the platform, it was placed on the platform by the experimenter. The rat remained on the platform for 45 s after reaching it. Day Three (Testing): The pool was filled to the same height, with the platform placed in the original location in the pool. Tempera paint was added and the rat was placed into one of the quadrants. Quadrant placement was counterbalanced across four trials. The amount of time it took the animal to find the hidden platform, and the distances traveled in the maze before finding it, were considered indices of performance on Day Three. On each trial, if the rat did not find the platform, it was placed on the platform by the experimenter. The rat remained on the platform for 45 s after reaching it. The mean latencies for rats to reach the platform across trials is indicated in insets in Figures 1, 3, and 5 to demonstrate learning curves for rats using this measure. During both training and testing, the distances swam in the pool and the latencies were used to calculate the average swim speed in each trial.

Bottom Line:
Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol).There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels.Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age.

Affiliation:
Department of Psychology, University at Albany-SUNY Albany, NY, USA.

ABSTRACTSome hippocampally-influenced affective and/or cognitive processes decline with aging. The role of androgens in this process is of interest. Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol). To determine the extent to which some age-related decline in hippocampally-influenced behaviors may be due to androgens, we examined the effects of variation in androgen levels due to age, gonadectomy, and androgen replacement on cognitive (inhibitory avoidance, Morris water maze) and affective (defensive freezing, forced swim) behavior among young (4 months), middle-aged (13 months), and aged (24 months) male rats. Plasma and hippocampal levels of androgens were determined. In experiment 1, comparisons were made between 4-, 13-, and 24-month-old rats that were intact or gonadectomized (GDX) and administered a T-filled or empty silastic capsule. There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels. Chronic, long-term (1-4 weeks) T-replacement reversed the effects of GDX in 4- and 13-month-old, but not 24-month-old, rats in the inhibitory avoidance task. Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age. Thus, age is associated with a decrease in 3alpha-diol production and 3alpha-diol administration reinstates cognitive and affective performance of aged male rats.